Methods for small incision eye surgery

ABSTRACT

Medical kits and methods for performing small incision DLEK include a corneal transplantation donor tissue graft formed into an implantable and compact rolled configuration using the flexible substrate.

RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.16/288,355, filed Feb. 28, 2019, which is a divisional of U.S. patentapplication Ser. No. 15/229,695, filed Aug. 5, 2016, now U.S. Pat. No.10,258,461, issued Apr. 16, 2019, which is a continuation of U.S. patentapplication Ser. No. 14/162,351, filed Jan. 23, 2014, now U.S. Pat. No.9,433,495, issued Sep. 6, 2016, which is a continuation of U.S. patentapplication Ser. No. 13/901,115, filed May 23, 2013, now U.S. Pat. No.8,673,002, issued Mar. 18, 2014, which is a continuation of U.S. patentapplication Ser. No. 11/626,959, filed Jan. 25, 2007, now U.S. Pat. No.8,470,029, issued Jun. 25, 2013, which claims the benefit of priority ofU.S. Provisional Application Ser. No. 60/762,452, filed Jan. 26, 2006,U.S. Provisional Application Ser. No. 60/788,221, filed Mar. 31, 2006,and U.S. Provisional Application Ser. No. 60/865,045, filed Nov. 9,2006, the contents of which are hereby incorporated by reference as ifrecited in full herein.

FIELD OF THE INVENTION

The invention relates to tools that facilitate corneal surgeries toimplant donor tissue.

BACKGROUND OF THE INVENTION

Conventional corneal transplantation surgery, also known as penetratingkeratoplasty, uses full-thickness corneal replacement with sutures.Recently, deep lamellar endothelial keratoplasty (DLEK) has been used toplace a partial-thickness corneal replacement from a healthy donorcornea into a host/recipient along with its endothelium. DLEK is alsoknown as “stitchless” corneal transplantation.

Some researchers and physicians believe that DLEK is a major advance inthe way that diseased human cornea is replaced with healthy donorcorneal endothelium. An exemplary transplantation procedure of aconventional donor harvesting and recipient preparation is described inThomas John, Stitchless Corneal Transplantation, Cataract & RefractiveSurgery Today, pp. 27-30, August 2004. As described, a donor cornealendothelium is coated with viscoelastic material and the cornea and itsattached scleral rim are placed in an artificial chamber. After excisionof the anterior stromal disc, the donor corneal stroma can be flipped onitself so that the donor corneal stroma rests on a Teflon® block withthe stromal side facing down and is held in place via vacuum.Trephination can be carried using a MORIA trephine. The deepstromal-endothelia donor disc can be carefully placed onto aviscoelastic-coated Ousley spatula (available from Bausch & Lomb) withthe endothelial side facing down.

More recently, a smaller incision DLEK technique has been proposed inwhich the donor disc (usually between about 8-8.25 mm in diameter) canbe held by simple forceps. In this procedure, the surgeon folds thetransplant in half (endothelial side down) and inserts the transplantmaterial through a 5 mm incision into the host anterior chamber (underair) and onto the host bed of the pre-resected central area.Instrastromal Cindy scissors can be used in a free hand manner to excisethe recipient disc using about an 8 mm circular ink mark on anepithelial surface as a visual template. A separate tool is typicallyused to manipulate the tissue into position. Once in the anteriorchamber, the folded donor disc is irrigated with saline to removeviscoelastic material, opened further with an air bubble (which can bedecreased in size), then rolled over the air bubble, thereby placing thedonor stromal surface into contact with the recipient stromal bed forself-adhesion. Staining of the donor disc can help a surgeon properlyalign the disc in the host bed. A reverse Sinskey hook can be used forfinal positioning to tuck the donor edges anterior to the recipient bededges to inhibit later dislodgement. See, Terry et al., Small IncisionDeep Lamellar Endothelial Keratoplasty (DLEK) Six Month Results in theFirst Prospective Clinical Study, Cornea, Volume 24, No. 1, pp. 59-65,January 2005.

Despite the foregoing, there is a need to provide surgical instrumentsthat can facilitate DLEK or stitchless corneal transplantation.

SUMMARY OF EMBODIMENTS OF THE INVENTION

Embodiments of the present invention are directed to devices and methodsthat can facilitate small incision DLEK and/or stitchless cornealtransplantation.

Some embodiments are directed to methods of configuring a deep stromalendothelial donor corneal disc (graft) for transplantation. The methodsinclude: (a) providing a corneal transplantation donor disc; and (b)rolling the disc into a compact implant configuration.

In some methods, the donor disk may have a diameter of between about 8mm to about 8.25 mm. The donor disc compact configuration may have across-sectional width that is less than about 3 mm (for example, about2.5 mm) suitable for entering a scleral access incision sized at lessthan about 4 mm (for example, about 3 mm).

In particular embodiments, the provided corneal donor disc has a firstunrolled generally planar configuration and the method can include: (a)providing a rolling tool having first and second cooperating membersthat define a gap space therebetween; (b) inserting a portion of theplanar donor disc between the first and second cooperating members; (c)forcing the first and second members together to trap a portion of thedonor disc therebetween; then (d) rotating the rolling tool to roll thedonor disc about itself.

Other embodiments are directed to surgical transplant donor corneal disckits. The kits include a rolled partial thickness donor cornealtransplant disc held in a sterilized package.

Yet other embodiments are directed to systems for performing smallincision DLEK. The systems include: (a) a rolled donor graft disc forendothelial replacement surgery; and (b) a rolled disc delivery devicefor releasably holding the rolled disc for surgical introduction in arecipient stromal bed via a small incision access site.

Some embodiments are directed to methods of configuring a deep stromalendothelial donor corneal tissue graft for transplantation. The methodsinclude: (a) providing a corneal transplantation donor tissue graft; (b)optionally placing the donor tissue graft on a flexible substrate; and(c) forming the donor tissue graft into a compact implantableconfiguration using the flexible substrate.

In some methods, the donor disk may have a diameter of between about 8mm to about 9 mm. The donor disc compact configuration may have across-sectional width that is less than about 3 mm (for example, about2.5 mm) suitable for entering a scleral access incision sized at lessthan about 4 mm (for example, about 3 mm).

Some embodiments are directed to surgical transplant donor corneal disckits that include a rolled partial thickness donor corneal transplantdisc held on a flexible substrate in a sterilized package.

In some embodiments, the kit can include a lubricant material disposedabout the rolled disc and the kit may also include a disc-holding memberconfigured to releasably hold the rolled disc.

Other embodiments are directed to corneal donor disc medical tools thatinclude: (a) a holding member with a holding chamber having a wall; and(b) a flexible substrate in cooperating relationship with the holdingchamber. The flexible substrate is configured to slidably enter theholding chamber and hold a corneal donor tissue graft in the holdingchamber in a rolled configuration.

The flexible substrate and/or the holding chamber can be configured toinhibit rotation of the tissue graft in the chamber so that a user cancontrol orientation of the stroma and endothelial sides of the implant.The tool can be single-use disposable.

Some embodiments are directed to donor harvesting tool kits thatoptionally include a flexible substrate. The kit holds a donor cornealgrafting disc in a rolled configuration for small incision DLEK. Thedonor disc can have a diameter between about 8-9 mm and a thicknessbetween about 100-200 μm.

Still other embodiments are directed to medical products with a rolleddonor corneal disc held on a flexible substrate for performing a smallincision DLEK.

Some embodiments are directed to systems for use in small incision DLEK.The systems include: (a) a rolled donor graft disc for endothelialreplacement surgery; and (b) a rolled disc delivery device forreleasably holding the rolled disc for surgical introduction in arecipient stromal bed via a small incision access site.

Some embodiments are directed to donor harvesting tools configured toreleasably engage and form a donor corneal grafting disc having adiameter between about 8-9 mm and a thickness between about 100-200 μm(typically about 150 μm) into a rolled configuration for small incision“stitchless” or self-healing DLEK. The harvesting tool can also be usedas the implantation tool (i.e., a dual-use single device). The donordisk may be held on a flexible substrate during surgical delivery.

Other embodiments are directed to methods for delivering donor tissue toan implantation site. The methods include: (a) holding the donor tissuein a rolled configuration on a flexible substrate in a cannula; (b)positioning the cannula at the target implantation site; then (c)slidably retracting the cannula and the flexible substrate away from theimplantation site, thereby releasing the donor tissue at theimplantation site.

Additional embodiments are directed to other methods for deliveringdonor tissue to an implantation site. The methods include: (a) holdingthe donor tissue in a rolled configuration in a cannula; (b) positioningthe cannula at the implantation site; then (c) pushing the donor tissueout of the cannula (typically by contact with a pushing member and/orfluid), thereby releasing the donor tissue proximate the implantationsite.

It is noted that any of the features claimed with respect to one type ofclaim, such as a system, apparatus, or computer program, may be claimedor carried out as any of the other types of claimed operations orfeatures.

Further features, advantages and details of the present invention willbe appreciated by those of ordinary skill in the art from a reading ofthe figures and the detailed description of the embodiments that follow,such description being merely illustrative of the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a schematic illustration of a medical tool according toembodiments of the present invention.

FIG. 1B is a schematic illustration of the device shown in FIG. 1Ashowing the flexible substrate and tissue graft being retracted into aholding chamber according to embodiments of the present invention.

FIG. 2 is a greatly enlarged cross-sectional view of the device shown inFIGS. 1A and 1B with a fully retracted flexible substrate with tissuegraft according to some embodiments of the present invention.

FIG. 3 is a flow chart of operational steps that may be taken to carryout embodiments of the present invention.

FIGS. 4A-4C are exemplary cross-sectional views taken along lines 4-4 inFIG. 5.

FIG. 5 is a partial side view of the device shown in FIGS. 1A and 1B.

FIG. 6 is a schematic side view of the device shown in FIG. 5illustrating an implant orientation of the tissue graft in the deviceaccording to some embodiments of the present invention.

FIGS. 7A-7C are side views of flexible substrates for receiving donortissue during a harvesting procedure according to some embodiments ofthe present invention.

FIGS. 8A and 8B are partial top views of exemplary flexible substrateconfigurations with releasable and integral arms, respectively,according to embodiments of the present invention.

FIGS. 9A-9C are top schematic views of exemplary flexible substrateconfigurations according to embodiments of the present invention.

FIG. 10A is a schematic top view of a flexible substrate with a collaraccording to some embodiments of the present invention.

FIG. 10B is a lateral section view of an anti-rotation configuration ofthe collar shown in FIG. 10A according to some embodiments of thepresent invention.

FIG. 10C is a partial longitudinal section view of an anti-rotationconfiguration to inhibit rotation of the substrate in the chamberaccording to embodiments of the present invention.

FIG. 10D is a lateral cross-sectional view of the device shown in FIG.10C illustrating a fin channel.

FIG. 11A is a schematic partial top view of another flexible substrateconfiguration according to embodiments of the present invention.

FIG. 11B is a greatly enlarged partial side view of a tissue graft onthe flexible substrate shown in FIG. 11A according to some embodimentsof the present invention.

FIG. 12 is a schematic partial top view of a holding device configuredto allow a user to view internal objects to visually confirm a desiredorientation of the transplant tissue graft according to embodiments ofthe present invention.

FIG. 13 is a schematic partial side view of a 2-way action medical toolaccording to some embodiments of the present invention.

FIG. 14 is a schematic partial side view of a one-way action medicaltool according to other embodiments of the present invention.

FIG. 15 is a schematic side view of a medical tool with a cooperatingflexible substrate according to embodiments of the present invention.

FIG. 16 is a schematic illustration of an exemplary donor harvestmedical kit according to embodiments of the present invention.

FIG. 17 is a schematic illustration of an exemplary medical kit with arolled donor disc preformed and ready for implantation according toother embodiments of the present invention.

FIGS. 18A and 18B are partial top views of the device shown in FIG. 1Aillustrating that the device may include visual orientation and/oralignment indicia according to embodiments of the present invention.

FIGS. 19A and 19B are perspective views of a flexible substrate showingthat the flexible substrate can be used to hold the donor tissue graftwith other medical tool configurations according to embodiments of thepresent invention.

FIGS. 20A-20C are schematic perspective views of a medical tool that canbe used to hold and/or deliver donor disc tissue according toembodiments of the present invention.

FIG. 21 is a schematic of an enlarged partial perspective view of thedevice shown in FIGS. 20A-20C.

FIG. 22 is a schematic illustration of a medical kit according toembodiments of the present invention.

FIG. 23 is a diagram of a data processing system that can be used toelectronically assist and/or control fluid pressure for delivery of thedonor disc according to some embodiments of the present invention.

FIG. 24A is a side perspective view of a medical rolling tool accordingto embodiments of the present invention.

FIG. 24B is an end view of the device shown in FIG. 24A illustrating agap space between upper and lower members according to some embodimentsof the present invention.

FIG. 25A is a side perspective view of the device shown in FIG. 24Aillustrating the device rolling a donor disc according to embodiments ofthe present invention.

FIG. 25B is an end view of the device shown in FIG. 25A, illustratingthe upper and lower members abutting each other according to someembodiments of the present invention.

FIGS. 26 and 27 are side perspective views of the device shown in FIGS.24A and 25A illustrating a sequence of operations used to roll the discinto a surgical preparation form according to embodiments of the presentinvention.

FIG. 28 is a side view of an exemplary surgical rolled donor discaccording to embodiments of the present invention.

FIG. 29 is a side perspective partial cutaway view of the tool androlled disc of FIG. 27 being placed in a surgical delivery toolaccording to some embodiments of the present invention.

FIG. 30 is a side partial cutaway view of the tool shown in FIG. 29illustrating the rolled donor disc held therein according to embodimentsof the present invention.

FIG. 31 is a side partial cutaway view of the tool shown in FIG. 30illustrating the donor disc being expelled from the chamber of thedelivery device according to some embodiments of the present invention.

FIG. 32A is a top view of the device shown in FIG. 31.

FIG. 32B is an end view of the device shown in FIG. 32A.

FIG. 33 is a schematic illustration of the device and rolled donor discbeing delivered to a recipient stromal bed to carry out a small incisionDLEK according to embodiments of the present invention.

FIG. 34 is a schematic illustration of an exemplary medical kit with arolled donor disc held by the rolling tool according to embodiments ofthe present invention.

FIG. 35 is a schematic illustration of another exemplary medical kitwith a rolled donor disc according to other embodiments of the presentinvention.

FIG. 36 is a schematic illustration of yet another medical kit with arolled corneal donor disc with a holding chamber according toembodiments of the present invention.

FIG. 37 is a schematic illustration of yet another medical kit with arolled corneal donor disc and delivery system according to embodimentsof the present invention.

FIG. 38 is a side cutaway view of another delivery device for a rolleddisc according to other embodiments of the present invention.

FIG. 39 is a side perspective partial cutaway view of the device shownin FIG. 29 illustrating that visual alignment indicia may be usedaccording to embodiments of the present invention.

DETAILED DESCRIPTION

The present invention now is described more fully hereinafter withreference to the accompanying drawings, in which embodiments of theinvention are shown. This invention may, however, be embodied in manydifferent forms and should not be construed as limited to theembodiments set forth herein; rather, these embodiments are provided sothat this disclosure will be thorough and complete, and will fullyconvey the scope of the invention to those skilled in the art.

Like numbers refer to like elements throughout. In the figures, thethickness of certain lines, layers, components, elements or features maybe exaggerated for clarity. Broken lines illustrate optional features oroperations unless specified otherwise. Features described or shown withrespect to one embodiment may be used with a different embodiment.

The terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting of the invention. Asused herein, the singular forms “a”, “an” and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. It will be further understood that the terms “comprises”and/or “comprising,” when used in this specification, specify thepresence of stated features, integers, steps, operations, elements,and/or components, but do not preclude the presence or addition of oneor more other features, integers, steps, operations, elements,components, and/or groups thereof. As used herein, the term “and/or”includes any and all combinations of one or more of the associatedlisted items. As used herein, phrases such as “between X and Y” and“between about X and Y” should be interpreted to include X and Y. Asused herein, phrases such as “between about X and Y” mean “between aboutX and about Y.” As used herein, phrases such as “from about X to Y” mean“from about X to about Y.”

Unless otherwise defined, all terms (including technical and scientificterms) used herein have the same meaning as commonly understood by oneof ordinary skill in the art to which this invention belongs. It will befurther understood that terms, such as those defined in commonly useddictionaries, should be interpreted as having a meaning that isconsistent with their meaning in the context of the specification andrelevant art and should not be interpreted in an idealized or overlyformal sense unless expressly so defined herein. Well-known functions orconstructions may not be described in detail for brevity and/or clarity.

It will be understood that when an element is referred to as being “on”,“attached” to, “connected” to, “coupled” with, “contacting”, etc.,another element, it can be directly on, attached to, connected to,coupled with or contacting the other element or intervening elements mayalso be present. In contrast, when an element is referred to as being,for example, “directly on”, “directly attached” to, “directly connected”to, “directly coupled” with or “directly contacting” another element,there are no intervening elements present. It will also be appreciatedby those of skill in the art that references to a structure or featurethat is disposed “adjacent” another feature may have portions thatoverlap or underlie the adjacent feature.

It will be understood that, although the terms first, second, etc. maybe used herein to describe various elements, components, regions, layersand/or sections, these elements, components, regions, layers and/orsections should not be limited by these terms. These terms are only usedto distinguish one element, component, region, layer or section fromanother region, layer or section. Thus, a first element, component,region, layer or section discussed below could be termed a secondelement, component, region, layer or section without departing from theteachings of the present invention. The sequence of operations (orsteps) is not limited to the order presented in the claims or figuresunless specifically indicated otherwise.

The term “rolled” and derivatives thereof refer to turning or coilingthe donor tissue about an axis into a substantially rolledconfiguration, thus inhibiting the formation of sharp fold edges. Theterms “small opening” or “small incision” means an opening that is lessthan about 5 mm wide and/or long, typically about 3 mm. The term“compact configuration” means that the donor disc is configured smallerthan its end use configuration by at least about 40%, typically lessthan about 50%. For example, if the end use configuration is about an8.25 mm diameter or width, then the compact configuration can provide awidth that about or less than about 5 mm, typically about or less than 4mm. In some configurations, the compact configuration can be about 60%less than the use or normal width, such as about 3 mm or less, and maybe about 2.5 mm.

Turning now to the figures, FIG. 1A illustrates a medical tool 10 and adonor tissue graft implant 25. The donor implant is typically a discsuch as a posterior lamellar keratoplasty transplant (PLK), althoughother tissue grafts, particularly fragile tissue grafts, may be suitablefor forming and/or delivery using devices/methods described herein. Asshown in FIG. 1A, in some embodiments, the tool 10 can cooperate with aflexible substrate carrier 15 that holds the implant 25. The holdingportion 15 e of the flexible substrate 15 can be configured to have asubstantially planar shape outside the tool 10.

As shown in FIGS. 1B and 2, the tool 10 has a cavity 10 c that isconfigured to slidably receive a flexible substrate carrier 15 thatholds the donor disc 25. As shown in FIG. 1B, as the flexible substrate15 enters (is retracted, withdrawn and/or pulled into) the tool cavity10 c, the outer edges of the flexible substrate 15 a, 15 b are pushedupward and can also be forced to travel closer together, thereby formingthe donor implant 25 into a smaller, typically compact, configurationusing the flexible substrate 15. The flexible substrate can beconformable so as to substantially conform to the shape of the cavitywall 10 w. As the flexible substrate 15 takes on a compactconfiguration, it forces the tissue graft 25 into a smaller, compactconfiguration.

As shown in FIG. 2, the flexible substrate 15 can be pushed, folded,wrapped or bent, and is typically formed to have a curvilinearcross-sectional shape 25 c with the two opposing edge portions spacedapart to define an open center space 25 g. However, the flexiblesubstrate 15 and donor tissue graft 25 can be formed into other shapes.The compact tissue graft shape can be a rolled shape without sharp foldcreases, corners or edges. As shown, the curvilinear shape 25 c can besubstantially oval with rounded lateral edges. The cavity 10 c can havea width W that is between about 3-6 mm, typically between about 3.5 mmto about 4 mm. The outside diameter (OD) of the disc in the shapedconfiguration 25 c can be between about 2.5 mm to about 3 mm, typicallyabout 2.87 mm for a 9 mm graft. The inside diameter (ID) of the shapeddisc 25 c can be between about 0.1 mm to about 0.5 mm less than the OD,depending on thickness of the graft 25. For the 2.87 mm OD and a tissuegraft having a thickness of about 150 μm, the ID can be about 2.84 mm.

FIG. 3 illustrates operational steps that can be used to configure adeep stromal endothelial donor corneal disc for transplantation. Acorneal transplantation donor tissue graft can be provided (block 70).The tissue graft can optionally be placed on a flexible substrate (block75), then the tissue graft can be formed into an implantableconfiguration using the flexible substrate (block 80). The forming canbe carried out substantially (if not totally) without endothelial celltrauma. FIG. 33 illustrates an exemplary target implantation site.

In some embodiments, the tissue graft has an endothelial side and anopposing stromal side, and the placing step is carried out so that thestroma side faces the flexible substrate with the endothelial sidefacing up (block 76). The holding member can be rotated so that thestromal side is facing upward and the endothelial side is facingdownward before inserting the tissue graft into a patient's targetanterior chamber (block 77).

In some embodiments, the tissue graft can be retracted on the flexiblesubstrate into a holding member with a cavity, the cavity having across-sectional width that is less than that of the flexible substrateand tissue graft, whereby the retracting step forces the flexiblesubstrate into the formed tissue graft implantable configuration (block78). In other embodiments, a supplemental tool can help form thesubstrate and disc into a compact configuration, independent of, outsideof and/or in cooperation with the holding member. The forming caninclude rolling the flexible substrate and tissue graft responsive tothe retracting step (block 79).

The flexible substrate 15 can be formed from a unitary layer ofbiocompatible material or laminated layers of biocompatible materials.The flexible substrate 15 can comprise any suitable biocompatiblematerial, such as elastomer, polymer, and copolymer materials and/orderivatives thereof, mylar, foil and the like, and/or combinationsthereof. Biocompatible non-stick and/or antifriction coatings may beused. The flexible substrate 15 can include a first anti-frictioncoating on one primary surface and a different coating on thetissue-contacting surface. The flexible substrate 15 can be a thin-filmsubstrate.

As shown in FIG. 2, the flexible substrate 15 can be thinner than thetissue graft 25. In some embodiments, the flexible substrate 15 is lessthan half the thickness of the graft 25. In particular embodiments, theflexible substrate 15 can be between about 1-200 μm thick, and moretypically between about 10-100 μm thick.

As shown in FIGS. 4A-4C, the curvilinear formed tissue graft shapes 25 cand flexible substrate 15 can be configured so that respective opposingedges are spaced apart with gaps 25 g, 15 g axially extending about amedial portion of the holding member cavity 10 c as shown in FIG. 4A.Alternatively, the substrate edges 15 a, 15 b may contact and evenoverlap as shown in FIG. 4B. Optionally, as shown in FIG. 4C, the disc25 may be rolled so that one edge 25 a is under the other edge 25 b. Itis noted that the cross-sectional shape of the holding cavity 10 c isshown in FIGS. 2 and 4A-4C as being substantially oval or circular;however, the instant invention is not limited thereto. Other geometricshapes may also be employed, such as, for example, pentagonal,hexagonal, square, rectangle, triangular, and the like.

FIG. 5 is a side view of the holding device 10 with the formed disc 25on the flexible substrate 15. As shown, the device 10 includes an angledor tapered forward edge portion 10 e to facilitate insertion into theanterior chamber during implantation and/or delivery. The height H ofthe cavity 10 c can be between about 3-6 mm, typically between about 3.5mm to about 4 mm. FIG. 5 also illustrates that a plunger 50 can bedisposed upstream of the formed disc 25. Fluid from the plunger 50and/or the plunger itself can be used to expel the tissue graft 25 fromthe cavity during surgical placement. Other irrigation deliveryconfigurations may also be used. In some embodiments, the flexiblesubstrate 15 is retained in the holding device 10 during delivery of thetissue graft 25. In other embodiments, the flexible substrate 15 can beadvanced with the disc during transplant placement in the eye.

FIG. 6 illustrates that the device 10 can have a harvest configurationand a delivery configuration with different orientations for holding andreleasing, respectively, the transplant tissue 25. As shown, it istypically desirable to have the endothelium side of the tissue facingupward and the stromal side oriented (facing) down during harvest orpreparation, and to reverse the orientation for ease of placement uponrelease of the implant from the cavity 10 c. As the implant leaves thecavity 10 c (after the device is inserted into a small incisionproximate the target anterior chamber bed), the disc 25 is no longerconstrained by the wall of the device 10 and can automatically unfold orunroll to a substantially planar configuration with the stroma sidefacing up.

FIGS. 7A-7C illustrate exemplary configurations of the flexiblesubstrate 15 when obtaining the donor tissue grant from a harvestingprocedure. The donor tissue graft 25 can be placed on the substrate 15when the carrier substrate is in the substantially planar configuration(FIG. 7A). In other embodiments, the carrier substrate 15 may beconfigured to have a concave or convex curvature as shown, for example,in FIGS. 7B and 7C, respectively. The donor graft 25 can be placed on anupper surface of the substrate 15, then formed into a more compactconfiguration. If concave or convex configurations are used, the formingmay follow the direction of the curvature. For example, the outer edges15 a, 15 b can be pushed upward for the configuration shown in FIG. 7Band the outer edges 15 a, 15 b can be pushed downward in the embodimentshown in FIG. 7C.

FIG. 8A illustrates that the flexible substrate 15 can be attached to anarm 16. The arm 16 can be rigid or have increased rigidity with respectto the flexible substrate 15. The arm 16 can be releasably attached tothe substrate 15 or fixedly attached to the substrate 15. FIG. 8Billustrates that the flexible substrate 15 can include an integral,rearwardly extending arm 15 r that extends away from the forward holdingportion of the substrate 15 e. The arm 15 r may be attached to astiffener member or may be laminated or otherwise structurallyreinforced for increased rigidity. The arm 15 r, 16 can engage theflexible substrate 15 and be used to pull the substrate into the cavityof the tool 10.

Typically, the donor disc 25 is placed on a first (upper) surface of theflexible substrate 15 with the stroma side contacting the substrate 15.The substrate 15 is then retracted into the holding cavity 10 c. Thedevice 10 is rotated, typically about 180 degrees, to place the stromaside up, with the endothelium side facing down. The end of the device 10e can be inserted into the eye's anterior chamber and the tissueejected, expelled or otherwise released.

FIGS. 9A-9C illustrate exemplary flexible substrate end portion (paddle)configurations 15 e. As shown in FIG. 9A, the flexible substrate 15 canhave an elongate body with a rounded arcuate forward edge portion 15 ethat merges into two parallel side portions. As shown in FIG. 9B, theflexible substrate forward edge portion 15 e can be substantiallycircular, and as shown in FIG. 9C, the forward edge portion 15 e can berectangular. The flexible substrates 15 can include visual alignmentindicia 18 for facilitating proper placement during the harvestingprocedure.

In some embodiments, the holding device 10 can be configured to inhibitrotation of the flexible substrate 15 inside the cavity 10 c topositively control and maintain the orientation of the flexiblesubstrate 15 as the tissue 25 is retracted and/or advanced. In thisarrangement, the stromal and endothelial sides are known and controlled,oriented to a user's control, and/or positioned so that the orientationfor placement can be easily determined or known.

FIG. 10A illustrates that the flexible substrate 15 can be configured toslidably retract into the tool body 10. The substrate 15 can be attachedto a collar 155 that can be angled and configured to slide in a singlecontrolled orientation within the cavity 10 c during advancement andretraction. In some embodiments, the substrate 15 can communicate withthe collar 155 to inhibit rotation inside the cavity 10 c and to allowthe substrate 15 to translate axially only in the retraction direction.As shown in FIG. 10B, the collar 155 can receive the plunger 50 andallow the plunger 50 to advance without advancing the flexible substrate15. In other embodiments, the substrate 15 can advance with the plunger50 and/or fluid to help position the disc 25 in a target location. Thecross-sectional shape of the plunger 50 can also be angled to be matablyreceived by the collar 155 to maintain the orientation of the plunger 50with respect to the flexible substrate 15 and/or cavity 10 c. Theplunger 50 may include fluid apertures (not shown) and/or fluid mayenter in advance of the plunger 50 and/or via the gap spaces between theplunger 50 and collar 155. The plunger 50 and/or fluid can be introducedover or under the arm 15 r to force the donor disc 25 from the cavity 10c with the flexible substrate 15 remaining in the cavity 10 c.

FIG. 10C illustrates an alternate exemplary anti-rotation configurationof the flexible substrate 15. As shown, the flexible substrate 15 caninclude at least one fin 15 f (shown as two) that can slide in a matingchannel/recess 10 ch (FIG. 10D) in the wall 10 w of the tool 10. Thechannel or recess 10 ch may alternatively reside in the substrate collar155 or other component rather than in the wall of the device.

FIG. 11A illustrates that the flexible carrier substrate 15 can includea well 19. The well 19 can be a depression formed in the substrate 15 oran aperture. The well 19 can reduce surface tension to facilitate theability of the flexible substrate 15 to roll or wrap to a compactconfiguration. FIG. 11B illustrates the donor tissue graft 25 placedover the well 19 prior to rolling or forming.

As noted above, the plunger 50 can be configured to advance based onpressurized fluid and/or rod actuation. If pressurized fluid alone isused, no separate plunger arm or plunger arm channel is required (notshown). In any event, where a plunger 50 is employed, the plunger 50 maybe configured directly (gently) contact a trailing edge of the rolleddisc 25 c, or may be configured to push indirectly, such as by pushingan intermediate fluid such as a gel (comprising, for example, aviscoelastic material) forward, thereby pushing the disc forward.

Alternatively, fluid can be introduced into the chamber 10 c anddirected to flowably expel the disc 25 c (FIG. 2) into position in theanterior chamber. The plunger 50 can be advanced to help expel the disc25 c as needed. The delivery device 10 can include a plurality of spacedapart flow orifices (and may include micronozzles) that are configuredto introduce fluid from a wall and/or from the plunger of the deviceinto the chamber 10 c. The orifices have an associated fluid channelthat can merge into the primary channel. The orifices can reside axiallyand circumferentially spaced apart about the chamber 10 c or may residesubstantially aligned in a rearward portion of the chamber 10 c to helpinitiate the expellant flow force onto the disc 25 c. The orifices maybe configured as flushing ports that can expel pressurized fluidgenerally inward and axially forward. Alternatively, the orifices can beconfigured to emit fluid under lesser pressures to inhibit adhesion tothe chamber walls.

FIG. 12 illustrates that the holding member 10 can be configured toallow a user to view internal components to observe orientation of thegraft and/or withdrawing, retracting, rolling and/or advancing action tovisually confirm orientation of the graft 25. The holding member 10itself can be visually transmissive, such as transparent or translucent,or may include at least one viewing window. If the latter, there aretypically at least two viewing windows, spaced apart so that one residesabove the other. As shown, a first viewing window 10 w (illustrated bythe cross-hatch markings) can axially extend over at least a majorportion of the length of the tissue graft 25, typically a substantiallength and with a width sufficient to allow a clinician to verify thatthe endothelial side is in position for implantation.

The tool 10 can be a multi-purpose, bidirectional tool that receivesdonor tissue, forms the donor tissue, holds the donor tissue, then isused to surgically deliver (expel) the donor implant 25.

It is contemplated that rolling the donor disc 25 can reduce damage tothe donor endothelium over folded configurations and/or provide forsmaller entry configurations. The donor disc 25 can have a typical usediameter that is between about 8.0 mm to about 9.0 mm, typically betweenabout 8.0 mm to about 8.25 mm; however, other suitable diameters may beused. The disc 25 may also have a thickness that is typically betweenabout 100-300 μm thick, and more typically between about 100-200 μmthick.

FIG. 13 illustrates that the plunger 50 and/or flexible substrate 15 canbe configured to operate with two-way action, while FIG. 14 illustratesthat the plunger 50 (and/or flexible substrate 15) can operate withone-way action. For the latter, the plunger 50 can translate to extend,whereas the flexible substrate 15 can translate to retract. Each mayhave a collar or other stop member that defines the stroke and/ordirectional travel.

FIG. 15 illustrates a thumb handle control actuator 110 with a fingerpost 110 f that can be used to operate the tool 10 during a surgicalprocedure. Turning the thumb handle control actuator 110 can retract theflexible substrate 15 into the tool cavity 10 c and/or push the plunger50 forward to expel the tissue graft 25 during surgical implantation.

The donor disc 25 can be extracted from the donor eye in any suitablemanner. Similarly, the desired size disc of the posterior corneal stromaof the recipient eye can be resected in any suitable manner, such as byusing instrastomal scissors (such as “Cindy Scissors” from Bausch &Lomb).

Typically, the tool 10 forms the disc 25 so that the lower donor stromalsurface is on the outside bottom surface of the rolled body 25 c (FIG.2).

To promote reliability, efficiency and/or ease in surgical placement, itis contemplated that a standard rolled orientation will be used and/orthat different medical kits noting the surgeon's desired rolledorientation can be provided. The latter can allow a surgeon to order akit that is suitable for the particular entry incision used (which mayvary depending on patient eye structure) and/or for a desired unrollingtechnique (side to side, top to bottom, bottom to top, offset, and thelike). The rolled disc 25 r may be configured for a temporal side or asuperior entry.

When unrolling in situ, rather than placing the rolled disc medially inthe recipient stromal bed, the rolled disc 25 r (FIG. 5) may be insertedcloser to a side edge portion of the eye, the side edge portiontypically being the one that corresponds to the last rolled portion. Thedonor disc can then be unrolled in an opposite direction using physicalor fluid forces.

To promote increased efficiency in surgical procedures, an OEM ormedical company can provide the donor disc 25 preformed in the rolledconfiguration 25 r (FIG. 5) and ready for surgery. The rolled disc 25 cmay be held in a refrigerated storage condition prior to end use. Thedisc 25 may be rolled using different end use disc sizes and provided ina preformed rolled configuration for different end use sizes (betweenabout 8 mm to about 9 mm, including about 8.25 mm).

The chamber 10 c has a length L sufficient to hold the length of thedisc 25 therein, and is typically between about 8.5-10 mm long,typically about 9 mm long. As noted above, pressurized fluid can beintroduced into the chamber 10 c to urge or force the rolled disc 25 cto exit the chamber. The fluid can comprise air, oxygen, saline, wateror other suitable fluid. Where a lubricant and/or viscoelastic substance(such as HEALON from Pharmacia in Nutley, N.J.) is used to preserve orprotect the rolled disc 25 r, a pre-delivery flushing may be desired toprepare the rolled disc 25 r for surgical insertion (to remove at leastsome of the substance from the rolled disc 25 r or chamber 10 c prior toplacement in the body). The open-end 10 e may be capped or sealed priorto use to help seal the disc in a sterile environment and/or placed in asterile sealed package.

FIG. 16 illustrates an example of a medical tool kit 200 that can beprovided to obtain donor tissue 25. The kit 200 includes a forming tool(holding member) 10 and a flexible substrate 15 in a sterile package 90.The kit 200 may also include fluid 21 that can be placed on the donortissue 25 before or after insertion into a holding member 10. The fluid21 can comprise a quantity of biocompatible liquid that can be placedabout the disc 25 in a sealable package. The liquid 21 can comprisesterile water, saline, viscoelastic material and the like.

FIG. 17 illustrates a medical kit 300 that includes a preformed(wrapped, folded and/or rolled) donor disc 25 c that may be releasablyheld in the holding member 10. The medical product 300 can be held in asterile package 90. The package 90 can be a flexible package, such as anelastomeric- or foil-backed elastomeric package, or a rigid substratepackage. Combinations of flexible and rigid packaging materials can alsobe used.

A fluid channel (conduit or other fluid channel configuration) can beprovided as a separate tool in the kit 300 or may be provided as one ofa standard component in a surgical suite. The fluid channel can beconfigured to engage a pressurized fluid flow source (such as a syringe,a cylinder, or other flow source) at a surgical site.

The kit 200, 300 and/or tool 10 can be labeled as single-use disposable.The tool 10 (at least the forward body thereof) can comprise asufficiently strong and relatively rigid elastomer, composite or ceramicor may comprise a metal, such as stainless steel. Combinations of thesetypes of materials may also be used. In other embodiments, the tool 10can be resiliently configured with sufficient structural rigidity tohold and form the disc 25 c.

FIGS. 18A and 18B illustrate that the combination harvesting tool anddelivery device 10 may be configured with visual alignment indicia 31 i,31 o. The alignment indicia 31 i, 310 can comprise arrows, text, coloror marked regions on an external viewable surface of the respectivedevices. For example, arrows or other indicia 31 i, 310 on a forwardportion of the holder body can help an operator retract (arrow in, 31 i)and implant (arrow out, 31 o) a disc 25 r in a desired orientation intothe anterior chamber. This can facilitate reliable and properpositioning for enhanced operative positioning of the disc in thestromal bed. In other embodiments, no indicia is needed on the deliverydevice 10 as the configuration can be visibly unique (i.e., the holdingmember body may be configured so that the implantation orientation isvisually different from a side or bottom portion) and the operator canalign the indicia 31 with the target orientation of the delivery device,based on the configuration of the body.

FIGS. 19A and 19B illustrate another embodiment of a tool 10′ that cancooperate with a flexible substrate 15 to form a donor disc 25 into acompact shape for implantation according to other embodiments of thepresent invention. As shown, two spaced apart prongs 12, 14 can hold theflexible substrate and tissue graft 25 and roll the tissue and substrateinto a desired configuration. A collar 30 can be advanced to lock thetool holding the rolled or formed tissue 25 and flexible substrate 15.

FIGS. 20A-20C illustrate another embodiment of a tool 10 that can holdand/or deliver the tissue 25 to a patient. As shown in FIG. 20A, thedevice 10 includes a carrier substrate 15 that is configured to hold thetissue graft 25. The carrier substrate 15 can be a biocompatible,pre-shaped carrier. The tissue graft 25 can be drawn into the cannula60, which can be described as a delivery barrel. The forward end portionof the cannula 60 can include a tapered end 10 e and can have a size(cross-sectional area and/or diameter) may allow for a self-sealingentrance wound, if desired.

As is also shown, the tool 10 includes a first cannula 60 (which candefine at least a portion of a holding chamber) that is configured toslidably receive and hold the carrier substrate 15, and a second cannula65 that is attached to the first cannula 60 and that can be configuredto slidably retract into the tool body 10 b. The tool 10 may alsoinclude a user slide control member 72 in communication with the carriersubstrate 15 and, optionally, the cannula 65.

As shown in FIG. 20B, the substrate 15 with the target implantationtissue 25 can be slidably retracted into the cannula 60 and held forsubsequent delivery to a patient in this configuration. A sterilecovering 90 (FIG. 22), such as a biocompatible, sterile pouch or bag,may be used to encase the loaded tool 10. The device 10 can be retainedin the retracted “hold” configuration and packaged in a sterile kit forlonger term storage and shipment, or the device 10 can be loaded andused at a single clinical site, even as preparation for and/or during apatient surgery.

FIG. 20C illustrates that, during actual implantation, once at a targetimplantation site, the second cannula 65 can be retracted substantiallyin concert with the substrate 15 to expose the tissue 25. As the firstcannula 60 is attached to the second cannula 65, the first cannula 60 isalso retracted, leaving the tissue 25 forward of the tissue deliverymember 150 and out of the device 10. This way a surgeon can orient theimplant tissue 25 (e.g., donor cornea) while held in the tool 10 insidethe eye in the cannula 60, and when the cannula 65 is retracted thetissue 25 remains substantially in the desired position at the targetimplantation site.

The slide control member 72 can be configured to translate from an empty(ready to load) position (FIG. 20A), to a retracted “hold” position(FIG. 20B), then to a second retracted “delivery” position (FIG. 20C).The slide control member 72 can be moved from the first to the secondposition to slide the tissue 25 on the substrate 15 into the firstcannula 60 while the first and second cannulas 60, 65 and tissuedelivery member 150 remain substantially stationary. During a surgicalprocedure, the slide control member 72 can be axially slid further awayfrom the patient, thereby retracting the first and second cannulas 60,65 and the substrate 15 and exposing the tissue 25. To inhibitinadvertent and/or premature release and/or exposure of the implanttissue 25 from the tool 10, the slide control member 72 can cooperatewith a locking member 73. The locking member 73 can be configured toinhibit further retraction of the substrate 15 as well as retraction ofthe cannulas 60, 65 and/or substrate 15 until actual delivery isdesired.

As shown in FIG. 21, the slide control member 72 can comprise a “thumb”or finger interface (e.g., a slide button or key) which is attached tothe substrate 15 with a slide extension 72 e. The tool body 10 b can beconfigured with a slot 73 s that slidably receives and matably holds thelock member 73 in position. The lock member 73 can be attached to thecannula 65 with an axially extending slide extension 61. To disengagethe lock member 73, a user can laterally move the lock member 73 out ofthe slot 73 s. The slide extension 72 e can be biased to axiallytranslate to allow a mating segment 72 m (such as a tab or protrusion)of the slide extension 72 e to engage the slide extension 61 (such asvia a mating slot or key form). The locking engagement of the slideextensions 72 e, 61 can maintain a desired alignment of the cannula(s)with the substrate and donor tissue 25. In operation, after the lockmember 73 is disengaged, as the slide control member 72 retracts, thesubstrate 15 and the cannulas 60, 65, retract substantially in concerttherewith.

In other embodiments, two separate slide controls may be used to retractthe cannulas 60, 65 and substrate 15 separately, either independently ordependently (not shown). Similarly, the lock member 73 can be configuredin other ways to inhibit premature sliding, such as, but not limited to,having a removable external locking ring that engages a stationary tab(not shown).

It is also noted that, instead of two cannulas 60, 65 as shown, forexample, in the embodiment in FIGS. 20A-20C, a single sliding cannulamay be used (not shown). If so, the single cannula may be stepped indiameter size (typically more narrow toward the penetration tip end). Inany event, in some embodiments, at least the forward portion of thefirst cannula 60 can be visually transmissive to allow a user to confirmthe position of the donor tissue and/or carrier substrate 15.

As shown in FIG. 20B, the tool 10 can also include a fluid deliverymember 150 held with an end portion residing inside the first cannula 60in communication (upstream but proximate to) with the implant material25. The tool 10 can be configured to provide flow-through irrigation viathe delivery member 150 that may be used to deploy tissue allograftand/or maintain chamber depth. In operation, the member 150 can beconfigured to remain substantially stationary both during initialloading of this carrier with tissue 25 into the cannula 60, and whilethe second cannula 65 and the first cannula 60 are axially retracted.The member 150 may be configured to facilitate the ejection of thetissue 25 from the tool 10. The member 150 may be configured to deliverpressurized fluid from the syringe 95 (FIG. 22). The member 150 cancontact the tissue 25 directly and/or flowably direct fluid to contactthe tissue 25. The member 150 can also deliver or push an intermediatefluid such as a gel (comprising, for example, a viscoelastic material)against a trailing edge of the tissue 25 to eject the tissue from thecannula 60 into a patient.

As shown in FIGS. 20A-20C, a proximal end portion of the device 10 p mayalso comprise a luer lock 74 configured to releasably and sealablyengage a syringe with sterile fluid (shown as feature 95 in FIG. 22).Sterile biocompatible fluid from the syringe 95 can be directed to flowthrough the device and exit the distal end portion of the device 10 d.As noted above, the fluid can be used to deploy the target tissue,maintain chamber depth, and/or introduce supplemental target material tofacilitate implantation, preparation and/or healing. The sterilebiocompatible fluid may comprise gas and/or liquid. The syringe 95 canbe used to flush the implant site prior to release of the target tissuedelivery, and the fluid for this purpose typically comprises saline. Thesyringe 95 may also optionally be used to “prime” the fluid channel (s)extending in the tool 10 to employ the sterile fluid to eject air fromthe fluid irrigation channel(s) prior to surgical penetration in thetarget body region. The tool 10 can be configured to accept differentfluids from different or the same syringe before or during theprocedure. The syringe 95 can be configured to hold and deliver throughthe tool 10 a therapeutic fluid treatment. The luer lock 74 can besealed closed prior to use to inhibit contamination (not shown).Similarly, a cap can be placed over the forward end of the tool 10 e(also not shown).

In some particular embodiments, the tool 10 can provide a surgeon withsubstantially atraumatic donor corneal tissue handling and may promoteprecision placement of donor corneal allograft in a recipient's anteriorchamber. The donor tissue can also be substantially atraumaticallyunsheathed in the recipient eye. As discussed above, the tool 10 can besingle-use disposable.

FIG. 22 illustrates another embodiment of a medical kit 400. Thismedical kit 400 can comprise the tool 10 (loaded or unloaded with thedonor tissue 25) and a biocompatible sterile 95 syringe. The syringe 95can be configured with a male luer lock 96 sized and configured tomatably engage with the female luer lock 74 on the tool 10. Eachcomponent may be held in sterile packaging 90.

FIG. 23 illustrates a data processing system that may be used to controlfluid delivery and/or plunger operation in some automated orsemi-automated delivery systems. Thus, as will be appreciated by one ofskill in the art, embodiments of the invention may be embodied as amethod, system, data processing system, or computer program product.Accordingly, particular embodiments of the present invention may takethe form of an entirely software embodiment or an embodiment combiningsoftware and hardware aspects, all generally referred to herein as a“circuit” or “module.” Furthermore, certain particular embodiments ofthe present invention may take the form of a computer program product ona computer-usable storage medium having computer-usable program codeembodied in the medium. Any suitable computer-readable medium may beutilized including hard disks, CD-ROMs, optical storage devices, atransmission media such as those supporting the Internet or an intranet,or magnetic or other electronic storage devices.

As such, computer program code for carrying out operations of thepresent invention may be written in an object oriented programminglanguage such as Java, Smalltalk or C++. However, the computer programcode for carrying out operations of the present invention may also bewritten in conventional procedural programming languages, such as the“C” programming language or in a visually oriented programmingenvironment, such as VisualBasic.

Certain of the program code may execute entirely on one or more of theuser's computer, partly on the user's computer, as a stand-alonesoftware package, partly on the user's computer and partly on a remotecomputer or entirely on the remote computer. In the latter scenario, theremote computer may be connected to the user's computer through a localarea network (LAN) or a wide area network (WAN), or the connection maybe made to an external computer (for example, through the Internet usingan Internet Service Provider). In some embodiments, some program codemay execute on local computers and some program code may execute on oneor more local and/or remote server. The communication can be done inreal time or near real time or off-line using a volume data set providedfrom the imaging modality.

The invention is described in part herein with reference to flowchartillustrations and/or block diagrams of methods, systems, computerprogram products and data and/or system architecture structuresaccording to embodiments of the invention. It will be understood thatsome blocks of the illustrations, and/or combinations of blocks, can beimplemented by computer program instructions. These computer programinstructions may be provided to a processor of a general-purposecomputer, special purpose computer, or other programmable dataprocessing apparatus to produce a machine, such that the instructions,which execute via the processor of the computer or other programmabledata processing apparatus, create means for implementing thefunctions/acts specified in the block or blocks.

These computer program instructions may also be stored in acomputer-readable memory or storage that can direct a computer or otherprogrammable data processing apparatus to function in a particularmanner, such that the instructions stored in the computer-readablememory or storage produce an article of manufacture includinginstruction means which implement the function/act specified in theblock or blocks.

The computer program instructions may also be loaded onto a computer orother programmable data processing apparatus to cause a series ofoperational steps to be performed on the computer or other programmableapparatus to produce a computer implemented process such that theinstructions which execute on the computer or other programmableapparatus provide steps for implementing the functions/acts specified inthe block or blocks.

As illustrated in FIG. 23, embodiments of the invention may beconfigured as a data processing system 116, which can be used tofacilitate or carry out delivery of the disc 25, and can include aprocessor circuit 100, a memory 136 and input/output circuits 146. Thedata processing system may be incorporated in, for example, the tool 10alone and/or one or more of a personal computer, workstation, server,router or the like. The processor 100 communicates with the memory 136via an address/data bus 148 and communicates with the input/outputcircuits 146 via an address/data bus 149. The input/output circuits 146can be used to transfer information between the memory (memory and/orstorage media) 136 and another computer system or a network using, forexample, an Internet protocol (IP) connection. These components may beconventional components such as those used in many conventional dataprocessing systems, which may be configured to operate as describedherein.

In particular, the processor 100 can be commercially available or custommicroprocessor, microcontroller, digital signal processor or the like.The memory 136 may include any memory devices and/or storage mediacontaining the software and data used to implement the functionalitycircuits or modules used in accordance with embodiments of the presentinvention. The memory 136 can include, but is not limited to, thefollowing types of devices: ROM, PROM, EPROM, EEPROM, flash memory,SRAM, DRAM and magnetic disk. In some embodiments of the presentinvention, the memory 136 may be a content addressable memory (CAM).

As further illustrated in FIG. 23, the memory (and/or storage media) 136may include several categories of software and data used in the dataprocessing system: an operating system 152; application programs 154;input/output device drivers 158; and data 156. As will be appreciated bythose of skill in the art, the operating system 152 may be any operatingsystem suitable for use with a data processing system, such as IBM®,OS/2®, AIX® or zOS® operating systems or Microsoft® Windows®95,Windows98, Windows2000 or WindowsXP operating systems Unix or Linux™.IBM, OS/2, AIX and zOS are trademarks of International Business MachinesCorporation in the United States, other countries, or both while Linuxis a trademark of Linus Torvalds in the United States, other countries,or both. Microsoft and Windows are trademarks of Microsoft Corporationin the United States, other countries, or both. The input/output devicedrivers 158 typically include software routines accessed through theoperating system 152 by the application programs 154 to communicate withdevices such as the input/output circuits 146 and certain memory 136components. The application programs 154 are illustrative of theprograms that implement the various features of the circuits and modulesaccording to some embodiments of the present invention. Finally, thedata 156 represents the static and dynamic data used by the applicationprograms 154 the operating system 152 the input/output device drivers158 and other software programs that may reside in the memory 136.

The data 156 may include (electronically stored) predefined flow modedata sets 126, such as a pre-delivery flow and an active delivery flowof one or more flow pressures and/or flow rates. As further illustratedin FIG. 23, according to some embodiments of the present inventionapplication programs 154 include a Flow Control or Fluid RegulatorModule 120. The application program 120 may be located in a local server(or processor) and/or database or a remote server (or processor) and/ordatabase, or combinations of local and remote databases and/or servers.

While the present invention is illustrated with reference to theapplication programs 154, 120 in FIG. 23, as will be appreciated bythose of skill in the art, other configurations fall within the scope ofthe present invention. For example, rather than being applicationprograms 120, 154 these circuits and modules may also be incorporatedinto the operating system 152 or other such logical division of the dataprocessing system. Furthermore, while the application program 120 isillustrated in a single data processing system, as will be appreciatedby those of skill in the art, such functionality may be distributedacross one or more data processing systems. Thus, the present inventionshould not be construed as limited to the configurations illustrated inFIG. 23, but may be provided by other arrangements and/or divisions offunctions between data processing systems. For example, although FIG. 23is illustrated as having various circuits and modules, one or more ofthese circuits or modules may be combined or separated without departingfrom the scope of the present invention.

As shown in FIG. 24A, as discussed with respect to FIGS. 19A and 19B,the medical tool 10 can have first and second cooperating elongatemembers 12, 14. The elongate members 12, 14 may have a length that isbetween about 6-15 mm, typically about 8-10 mm. As shown, the tool 10receives a side edge portion of the disc 25 as shown in FIG. 24A. Asshown in FIG. 24B, the distal edges of the members 12, 14 can be spacedapart by a distance 16 during the initial positioning. The distance 16can be greater than the thickness of the donor disc 25. To provide foradequate separation and disc thickness variation, the distance 16 may beat least about 300 μm, typically between about 300-600 μm thick.However, other separation distances in the open configuration shown inFIGS. 24A and 24B may also be used. In this embodiment, the tool 10 canbe described as a rolling tool 10 that rolls the disc 25 so that thelower donor stromal surface is on the outside surface 25 e of the rolledbody 25 r (FIG. 28). In the embodiment shown in FIGS. 24A, 24B, noflexible substrate carrier is required. Also, the donor disc 25 can berolled from a top edge portion toward a bottom edge portion. However,other rolled orientations can also be used (and the upper donor stromamay be on the outside of the rolled body).

As shown in FIGS. 25A and 25B, the elongate members 12, 14 also have aclosed configuration whereby the members 12, 14 close to clamp or trap aside edge portion of the donor disc therebetween. In operation, a sleeve30 can axially slide forward to force the members 12, 14 together.Typically, the members 12, 14 gently contact when in the closedconfiguration without the disc 25 therebetween as shown in FIG. 25B.FIGS. 26 and 27 illustrate that after the sleeve 30 is moved forward toclose the members 12, 14 together with the side edge portion of the disc25 therebetween, the tool 10 can be rotated one or more times to formthe disc 25 into a rolled compact configuration as shown in FIG. 28. Inthis exemplary configuration, the disc 25 can have a rolled body 25 rthat has a length that is between about 8-8.25 mm and a width W (orheight) of less than about 3 mm, typically about 2.5 mm.

During the rolling, the members 12, 14 are spaced apart and gentlycontact the disc 25 in a manner that allows the members 12, 14 to holdthe disc 25 during rolling without imparting undue force on theendothelial cells to inhibit cellular injury.

Other tool configurations may be used to roll the disc into the desiredconfiguration. For example, in some embodiments, an end cap or end clamp(not shown) can be used to force the members 12, 14 together (notshown). Similarly, the distal end of the tool may have a closed endrather than an end that can open and close, and the disk 25 can beinserted in between the two members 12, 14 (also not shown). It is alsocontemplated that a different roller tool configuration can be used,such as a single member (rather than cooperating spaced apart members)that can roll the disc (not shown). For example, a single member maycooperate with a separate tool or even manual manipulation until a firstroll is started, and/or the tool may even employ a gentle biocompatible(liquid) adhesive.

Although the tool 10 is particularly suitable for rolling the disc 25,the tool 10 can be used to fold or otherwise hold the disc 25 as well.That is, it is contemplated that the tool 10 can fold the body of thedisc with a lesser likelihood of endothelial damage compared to forcepswhere the force applied is less controlled. Indeed, the tool 10 may beused to hold the disc 25 in larger configurations for larger incisionplacement.

The elongate members 12, 14 can have a rounded cross-sectional shape andmay have a smooth resilient contact surface, and may have a resilientbody with sufficient rigidity to hold the disc during the rollingoperations. The elongate members 12, 14 may comprise, for example, foam,sponge, cellulose, elastomer or polymer. The elongate members 12, 14 mayalso be formed of metal. The members 12, 14 may include surface coatingsthat inhibit slipping or provide lubricity to inhibit contact damage.

To promote reliability, efficiency and/or ease in surgical placement, itis contemplated that a standard rolled orientation will be used and/orthat different medical kits noting the surgeon's desired rolledorientation can be provided. The latter can allow a surgeon to order akit that is suitable for the particular entry incision used (which mayvary depending on patient eye structure) and/or for a desired unrollingtechnique (side to side, top to bottom, bottom to top, offset, and thelike). The rolled disc 25 r may be configured for a temporal side or asuperior entry.

When unrolling in situ, rather than placing the rolled disc medially inthe recipient stromal bed, the rolled disc 25 r (FIG. 5) may be insertedcloser to a side edge portion of the eye, the side edge portiontypically being the one that corresponds to the last rolled portion. Thedonor disc can then be unrolled in an opposite direction using physicalor fluid forces.

To promote increased efficiency in surgical procedures, an OEM ormedical company can provide the donor disc 25 preformed in the rolledconfiguration 25 r (FIG. 28) and ready for surgery. The rolled disc 25 rmay be held in a refrigerated storage condition prior to end use. Thedisc 25 may be rolled using different end use disc sizes and provided ina pre-formed rolled configuration for different end use sizes (about 8mm and about 8.25 mm).

FIG. 29 illustrates that, in some embodiments, the rolling tool 10 caninsert the rolled disc 25 r into a discrete delivery device 250. Inother embodiments, the tool 10 can hold the rolled disc 25 r duringimplantation and hence, be the delivery device. As shown in FIG. 29, thedelivery device 250 has a holding chamber 51 with a forward open portion52; the forward portion 52 may have a beveled shape as shown. Thechamber 51 is in fluid communication with a fluid source 75 (FIG. 31).The device 250 may also include a plunger 60.

In some embodiments, after the tool 10 enters the chamber 51, the sleeve30 is retracted, thereby depositing the disc in the chamber 51. The tool10 can be removed from the device 250. The tool 10 can be sterilized forre-use or be single-use disposable. As shown in FIG. 30, the rolled disc25 r is held in the chamber 51. The chamber 51 can have a width We thatis between about 2.75 mm to about 5 mm, typically between about 3-4 mmwide, and in some embodiments about 3 mm wide. The chamber 51 has alength L sufficient to hold the length of the disc 25 therein, and istypically between about 8.5-10 mm long, typically about 9 mm long.Pressurized fluid can be introduced into the chamber 51 to urge or forcethe rolled disc 25 r to exit the chamber 51. In some embodiments, asshown in FIG. 31, a perforated plunger 60 can be advanced to help expelthe disc 25 from the chamber 51. The plunger 60 can allow fluid to enterthe chamber through perforations or openings 66 in the plunger body. Thefluid can comprise air, oxygen, saline, water or other suitable fluid.The openings 66 can be on the plunger head and/or via the arm 62. Adifferent fluid can be introduced via the channel or opening in the arm62. For example, air can be introduced through the arm 62 while a liquidcan be introduced via side openings 66. Where a lubricant and/orviscoelastic substance (such as HEALON from Pharmacia in Nutley, N.J.)is used to preserve or protect the rolled disc 25 r, a pre-deliveryflushing may be desired to prepare the rolled disc 25 r for surgicalinsertion (to remove at least some of the substance from the rolled disc25 r or chamber 51 prior to placement in the body).

The plunger 60 can be configured to allow a surgeon to manually advancethe plunger 60 using the plunger arm 62, and the fluid source 75 may bedirected to flow to the chamber 51 from a channel 53 that merges intothe channel 63 in which the plunger arm 62 travels. FIG. 32A illustratesthe device 250 with two paths 53, 63 and FIG. 32B illustrates the openend 52 of the device 250. This open end 52 may be capped or sealed priorto use to help seal the disc in a sterile environment.

In other embodiments, the plunger 60 can be configured to advance basedon the pressurized fluid 75 and no separate plunger arm or plunger armchannel is required (not shown). In such a case, the channel 53 can be astraight channel (such as the plunger arm channel 63) to inhibitpressure drops. In any event, where a plunger 60 is employed, theplunger 60 may be configured to push indirectly, such as by pushing anintermediate fluid such as a gel (comprising, for example, aviscoelastic material) forward, thereby pushing the disc forward, or maydirectly (gently) contact the trailing edge of the rolled disc 25 r.

FIG. 33 illustrates an exemplary surgical introduction of the device 250to insert the rolled disc 25 r into position in a recipient. As shown,fluid can be introduced into the chamber 51 and directed to flowablyexpel the rolled disc into position. The plunger 60 can be advanced tohelp expel the disc 25 r as needed. FIG. 36 illustrates that thedelivery device 250′ can include a plurality of spaced apart floworifices 54 (and may include micronozzles) that are configured tointroduce fluid from a wall of the device into the chamber 51. Theorifices 54 have an associated fluid channel 55 that can merge into theprimary channel 63. The orifices 54 can reside axially andcircumferentially spaced apart about the chamber 51 or may residesubstantially aligned in a rearward portion of the chamber 51 to helpinitiate the expellant flow force onto the disc 25 r. The orifices 54may be configured as flushing ports that can expel pressurized fluidgenerally inward and axially forward. Alternatively, the orifices 54 canbe configured to emit fluid under lesser pressures to inhibit adhesionto the chamber walls.

FIGS. 34-37 illustrate examples of preformed donor discs 25 provided asa medical product or kit 90. The reference number 90 is used togenerally denote the medical product, but with respect to eachembodiment in FIGS. 34-37, an alphabetical suffix is used todifferentiate the specific product embodiment therein (i.e., 90 a, 90 b,90 c, 90 d). The medical product 90 can be held in a sterile package 91.The package 90 can be a flexible package, such as an elastomeric- orfoil-backed elastomeric package, or a rigid substrate package.Combinations of flexible and rigid packaging materials can also be used.A quantity of biocompatible liquid 92 can be placed about the disc 25 inthe package 91. The liquid 92 can comprise sterile water, saline,viscoelastic material and the like.

FIG. 34 illustrates that the product 90 a comprises a holding device(shown as the rolling tool itself) and the rolled disc 25 r. FIG. 35illustrates that the product 90 b can be the rolled disc alone in thepackage 91. FIG. 36 illustrates that the product 90 c can be a deliverytool 250 with the rolled disc 25 r already in position therein. A fluidchannel (conduit or other fluid channel configuration) can be providedas a separate tool in a kit or may be provided as standard components ina surgical suite. FIG. 37 illustrates the delivery device 250 and rolleddisc 25 r as well as a length of rigid flow pipe and/or flexible flowchannel 53 that is configured to engage a pressurized fluid flow source(such as a syringe, a cylinder, or other flow source) at a surgicalsite.

In the product 90, the delivery device 250 and/or tool 10 can be labeledas single-use disposable. The portions of the product 90 that contactthe body should be made from a biocompatible material and/or comprise abiocompatible coating.

The tool 10 and/or delivery device 250 (at least the forward bodythereof) can comprise a sufficiently strong and relatively rigidelastomer, composite or ceramic or may comprise a metal, such asstainless steel. Combinations of these types of materials may also beused. In other embodiments, the tool members 12, 14 can be resilientlyconfigured with sufficient structural rigidity to hold and form therolled disc 25 r.

FIG. 38 illustrates that the delivery device 250″ may be resilientlycompressible as represented by the arrows on each side of the devicebody. In operation, the outer wall 250 w forming the chamber 51 can becompressed or pushed together to urge the disc 25 r out of the chamber51. In operation, a clinician can compress a rearward portion of thechamber 51 and work his or her way forward to squeeze or urge the discout of the chamber. The device 250″ may be configured to expel the disc25 r out and into position in the eye using only the compressibility ofthe walls, or the device 250″ may be optionally configured to alsoemploy a plunger and/or pressurized fluid as for the embodiments notedabove. The device chamber 51 can be defined by a plasticized polymer orother suitable elastomeric material.

FIG. 39 illustrates that the rolling tool 10 or the delivery device250′″ (which can be used with any delivery device, such as embodiments250, 250′, 250″) may be configured with visual alignment indicia 31,151. The alignment indicia 31, 151 can comprise arrows, color or markedregions on an external viewable surface of the respective devices. Forexample, arrows or other indicia 31 on the sleeve 30 or forward portionof the body, such as a forward visible portion of members 12, 14, canhelp an operator insert the rolled disc 25 r in a desired orientationinto the chamber 51. This can facilitate reliable and proper positioningfor enhanced operative positioning of the disc in the stromal bed.Similarly, visual indicia marking 151 on the delivery device 50′″ canfacilitate proper orientation with the incision cite and/or alignmentwith the tool 10 and/or 250. In other embodiments, no indicia is neededon the delivery device 250 as the configuration can be visibly unique(i.e., the top is visually different from a side or bottom portion) andthe operator can align the indicia 31 with the target orientation of thedelivery device, based on the configuration of the body.

The foregoing is illustrative of the present invention and is not to beconstrued as limiting thereof. Although a few exemplary embodiments ofthis invention have been described, those skilled in the art willreadily appreciate that many modifications are possible in the exemplaryembodiments without materially departing from the novel teachings andadvantages of this invention. Accordingly, all such modifications areintended to be included within the scope of this invention as defined inthe claims. The invention is defined by the following claims, withequivalents of the claims to be included therein.

That which is claimed:
 1. A method for delivering donor corneal tissueto an implantation site, comprising: providing a delivery device with acannula holding the donor corneal tissue in a rolled configuration on aflexible substrate in the cannula; positioning the cannula at theimplantation site; and inserting the donor corneal tissue at theimplantation site by retracting the cannula relative to the flexiblesubstrate or by extending the flexible substrate out of the cannula torelease the donor corneal tissue at or proximate the implantation site.2. The method of claim 1, wherein the delivery device has a first endportion that holds the flexible substrate therein and an opposing secondend portion that is longitudinally spaced apart from the first endportion, and wherein the second end portion is configured to couple to aliquid source, the method further comprising directing liquid from theliquid source though the cannula and out the first end portion of thedelivery device during the positioning and/or inserting step.
 3. Themethod of claim 2, wherein the first end portion of the delivery devicecomprises a cavity having a cross-sectional width that is less than awidth of the flexible substrate as measured when the flexible substrateis external to the delivery device.
 4. The method of claim 1, whereinthe donor corneal tissue has an endothelial side and an opposing stromalside, and wherein the stromal side faces the flexible substrate.
 5. Themethod of claim 4, further comprising orienting the cannula so that thestromal side faces up and the endothelial side faces down beforereleasing the donor corneal tissue from the cannula.
 6. The method ofclaim 1, wherein the positioning is carried out by placing the cannulainto a target anterior chamber of an eye of a patient to theimplantation site.
 7. The method of claim 1, wherein the flexiblesubstrate has a well, an aperture or a portion with reduced rigidity topromote rolling of the flexible substrate and the donor corneal tissueheld thereon.
 8. The method of claim 1, wherein the donor corneal tissueis a donor disk, and wherein a distal end of the cannula has a width ina range of about 3 mm to about 4 mm.
 9. The method of claim 1, whereinthe positioning is carried out by placing the cannula into a scleralaccess incision sized at less than about 4 mm.
 10. The method of claim1, wherein the inserting is carried out so that upon release the donorcorneal tissue unrolls to a generally planar configuration.
 11. Themethod of claim 1, further comprising flowing pressurized liquid from aliquid source in fluid communication with the cannula during thepositioning and/or inserting.
 12. The method of claim 11, wherein thepressurized fluid is flowed axially into the cannula and out of a distalend of the cannula to thereby facilitate placing the rolled donorcorneal tissue into a host bed of an eye of the patient at theimplantation site.
 13. The method of claim 1, wherein the insertingcomprises advancing a plunger into the cannula to help expel the rolleddonor corneal tissue out of the cannula.
 14. The method of claim 1,wherein the rolled donor corneal tissue has a substantially cylindricalshape with a cross-sectional diameter that is less than about 4 mm, andwherein the method is carried out for small incision endothelialkeraloplasty.
 15. The method of claim 1, wherein the delivery devicecomprises orientation indicia, and wherein the method further comprisesorientating the cannula into a proper orientation using the orientationindicia during or before the positioning.
 16. The method of claim 1,wherein the cannula comprises first and second cooperating cannulas, atleast one of which is axially slidably extendable and/or retractablerelative to the other, and wherein the inserting is carried out byslidably extending and/or retracting the first and/or second cannulaaxially to release the rolled donor corneal tissue.
 17. The method ofclaim 1, wherein the delivery device comprises an external user inputmember that slides axially to cause the cannula to release the rolleddonor corneal tissue.
 18. A method for delivering a tissue graft to animplantation site in an eye of a patient, comprising: providing adelivery device comprising an elongate tubular body having opposingfirst and second end portions and a control mechanism, the first endportion having a leading forward open end with a width that is betweenabout 3 mm to about 6 mm, wherein the second end portion of the elongatebody is configured to releasably engage a fluid source, and wherein thetissue graft is held on a flexible substrate in a rolled configurationin the first end portion of the delivery device; flowing irrigationfluid through the delivery device into an anterior chamber of the eye ofthe patient during implantation of the tissue graft; moving the controlmechanism of the delivery device to release the rolled tissue graft fromthe first end portion of the delivery device into the anterior chamberof the eye at the implantation site while the fluid is flowed out of thedelivery device into the anterior chamber of the eye.
 19. The method ofclaim 18, wherein the control mechanism moves axially and releases therolled tissue graft by either (i) retracting a cannula, defining thefirst end portion of the delivery device or that is coupled to the firstend portion of the delivery device, relative to the flexible substrateor (ii) extending the flexible substrate with the rolled tissue graftout of the cannula.
 20. The method of claim 18, wherein, in response tomovement of the control mechanism by a user, the tissue graft isatraumatically unsheathed from the first end portion of the deliverydevice while the flexible carrier substrate remains in the deliverydevice.
 21. The method of claim 18, wherein the first end portion of thedelivery device includes a first cannula attached to a second cannulathat is concentrically aligned with and behind the first cannula, andwherein the first and/or second cannula is axially retractable and/orextendable.
 22. The method of claim 18, wherein the elongate tubularbody has an externally accessible slot that engages a lock member thatis in communication with the control mechanism to inhibit retraction ofthe first cannula, the method further comprising releasing the lockmember before moving the control mechanism longitudinally in the slot.23. The method of claim 18, wherein the leading forward open end istapered.
 24. The method of claim 18, wherein the implantation is carriedout as a small incision endothelial keraloplasty treatment.